This application describes a comprehensive research project designed to prospectively examine the efficacy of cortisol treatment, initiated within twelve hours of a traumatic event, at preventing the subsequent development of PTSD symptoms in hospitalized trauma victims. Previous research has found that trauma victims who develop PTSD excrete lower levels of urinary cortisol in the immediate aftermath of the trauma than victims who do not develop PTSD. In addition, theoretical and empirical research in both animal and human samples has suggested mechanisms through which altered cortisol levels can affect memory formation. Low levels of cortisol may lead to aberrant memory formation and "overconsolidated" memories. These memories may then manifest themselves in the intrusive thoughts and hyperarousal symptoms characteristic of PTSD. Increasing levels of cortisol during and following emotionally-arousing events may protect against the development of PTSD. Recent pre-clinical research has found that sepsis and cardiac surgery patients who have cortisol levels elevated through the administration of hydrocortisone have a lower incidence of PTSD than patients who do not receive hydrocortisone. This suggests that exogenously administering hydrocortisone may prevent or buffer the development of PTSD symptoms in trauma victims. However, this hypothesis has not been tested in a randomized, double-blind, controlled trial of heterogeneous trauma victims. The proposed research will examine 52 trauma victims who require admission to a local Level 1 trauma center. Participants will be randomly assigned to a 10-day medication regimen (plus taper) consisting of either cortisol or placebo. Follow-up time points at one and three months will consist of interviews and questionnaires designed to measure symptoms of PTSD and comorbid disorders. Further, urinary cortisol levels will be measured to examine the effects of early cortisol treatment on basal hormone levels. The proposed research will directly test the efficacy of early cortisol treatment at preventing symptoms of PTSD and comorbid disorders and will provide pilot data and estimates of effect sizes for a large-scale randomized, double-blind trial.